title: Suppression of TRIF-dependent signaling pathway of toll-like receptors by (E)-1-(2-(2-nitrovinyl)phenyl)pyrrolidine.
abstract: Toll-like receptors (TLRs) play an important role in the recognition of microbial pathogens and induce innate immune responses. The recognition of microbial components by TLRs triggers the activation of myeloid differential factor 88 (MyD88)- and toll-interleukin-1 receptor domain-containing adapter inducing interferon-β (TRIF)-dependent downstream signaling pathways. Previously, we synthesized (E)-1-(2-(2-nitrovinyl)phenyl)pyrrolidine (NVPP), which contains a nitrovinyl-phenyl and pyrrolidine. To evaluate the therapeutic potential of NVPP, its effect on signal transduction via the TRIF-dependent pathway of TLRs induced by lipopolysaccharide (LPS) or polyinosinic-polycytidylic acid (poly[I:C]) was examined. NVPP inhibited LPS or poly[I:C]-induced activation of nuclear factor-κB (NF-κB) and interferon regulatory factor 3 (IRF3), and the phosphorylation of IRF3, as well as inhibiting the activation of interferon-inducible genes such as interferon inducible protein-10 (IP-10). These results suggest that NVPP can modulate TRIF-dependent signaling pathways of TLRs, potentially resulting in effective therapeutics for chronic inflammatory diseases.
authors.affiliation: Department of Biomedical Laboratory Science, College of Medical Sciences, SoonChunHyang University, Chungnam, Asan 336-745, Republic of Korea.
authors.forename: Gyo-Jeong
authors.initials: GJ
authors.lastname: Gu
authors.forename: Sang-Hoon
authors.initials: SH
authors.lastname: Eom
authors.forename: Chang Won
authors.initials: CW
authors.lastname: Suh
authors.forename: Kwang Oh
authors.initials: KO
authors.lastname: Koh
authors.forename: Dae Young
authors.initials: DY
authors.lastname: Kim
authors.forename: Hyung-Sun
authors.initials: HS
authors.lastname: Youn
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D011759:Pyrrolidines / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D013343:Styrenes / Q000494:pharmacology*; D051193:Toll-Like Receptors / Q000378:metabolism*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D000893:Anti-Inflammatory Agents; D053594:Myeloid Differentiation Factor 88; D011759:Pyrrolidines; D013343:Styrenes; D051193:Toll-Like Receptors; C587911:1-(2-(2-nitrovinyl)phenyl)pyrrolidine; C476286:Ticam1 protein, mouse
keywords: (E)-1-(2-(2-nitrovinyl)phenyl)pyrrolidine; Interferon regulatory factor 3; Lipopolysaccharide; Polyinosinic-polycytidylic acid; Toll-like receptor